Cardiac Contractility Recovery, CD34+ Stem Cells, Heart Failure, Microvascular Dysfunction, Tako Tsubo Cardiomyopathy
Conditions
Keywords
Takotsubo syndrome, CD34+ stem cells, heart failure, microvascular dysfunction, cardiac contractility recovery
Brief summary
The underlying mechanisms of microvascular dysfunction in Takotsubo cardiomyopathy remain incompletely understood. As CD34+ cells are essential to coronary microvascular homeostasis we will investigate the potential association between CD34+ cell count and changes in left ventricular function in patients with Takotsubo cardiomyopathy at baseline and 6-month follow-up.
Detailed description
Takotsubo syndrome presents with a transient non-ischemic acute heart failure and relatively fast recovery of myocardial contractility. This medical condition is often precipitated by a previous trigger, such as physical or emotional stress. However, in approximately one-third of Takotsubo patients, the trigger remains unidentified. In terms of acute clinical presentation, Takotsubo patients with and without acute coronary syndrome-related symptoms have been recognized. Early recognition of the latter group is challenging due to the lack of clear indication for transthoracic echocardiography and coronary angiography with left ventriculography in this patient cohort, representing the gold standard in diagnostics of Takotsubo patients. Therefore, the prevalence of Takotsubo patients without acute coronary syndrome-related symptoms appears to be underestimated. In addition, novel data reveal that both short- and long-term prognoses in Takotsubo patients are comparable to the prognosis in acute coronary syndrome patients. Furthermore, chronic heart failure has been recognized in a subgroup of Takotsubo patients. To sum up, Takotsubo syndrome represents a heterogeneous medical condition, with a potential for adverse outcomes. This calls for new approaches to the diagnostics and treatment of this patient population. Coronary microvascular dysfunction has been proposed as a crucial pathophysiological mechanism underlying Takotsubo pathogenesis, including the left ventricular dysfunction at acute episode and the degree/rate of left ventricular contractility improvement. As CD34+ cells are essential to coronary microvascular homeostasis we speculated on potential association between CD34+ cell count and changes in left ventricular function in patients with Takotsubo cardiomyopathy at baseline and 6-month follow-up. In this single-center prospective pilot cohort study we included 34 consecutive patients with Takotsubo cardiomyopathy treated at our center between September 2021 and January 2026. Patients with a history of malignancy and concurrent acute coronary syndrome-mimicking conditions (myocardial infarction, myocarditis, etc) were not considered for this analysis. Takotsubo cardiomyopathy diagnosis was established per InterTac Registry criteria. Patients were enrolled within 24h of admission and underwent comprehensive clinical examination, blood biochemical and hematological analysis, and echocardiography at baseline and 6-month follow-up. Additionally, we expect at least half of the enrolled patients to complete cardiac MRI scan at baseline and 6-month follow-up. CD34+ cell count was measured using Beckman-Coulter Navios EX flow cytometry with standard antibodies according to ISAGE protocol. The study results might enhance undertsanding of the pathophgysiological mechanism underlying structural and functional myocardial recovery among Takotsubo patients. Also, the study outcomes might provide crucial context for justifying further research work on investigating potential therapeutic effects of CD34+ cells on myocardial contractility recovery among Takotsubo patients.
Interventions
None listed
Sponsors
University Medical Centre Ljubljana
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Minimum age 18 years * Established TTS per InterTak registry criteria * Signed consent form
Exclusion criteria
* Patients under the age of 18 years * Ischemic heart disease with at least one complete total occlusion * Other concurrent cardiomyopathies * Active infectious myocarditis * obstructive coronary artery disease * Previous hospital stay due to acute coronary syndrome (myocardial infarction) in the last 6 months before TTS acute event * Previous interventional coronary artery procedure in the last 6 months before TTS acute event * Significant valvular heart disease * Significant peripheral artery occlusive disease * Active or remitted hematologic malignancy * Patients receiving immunosuppressive therapy * Significant comorbiditeis affecting patients survival (malignancy) * Failure to obtain freely given, informed consent form.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recovery of left ventricular systolic function assessed by change in left ventricular ejection fraction (LVEF) | From enrollment to the end of observational period at 6-month follow-up. | Change in LVEF (%), measured by transthoracic echocardiography using Biplane Simpson's method. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in myocardial contractility and deformation assesed by change in left ventricular global longitudinal strain (LV GLS) | From enrollment to the end of observational period at 6-month follow-up. | Change in LV GLS (%), measured by transthoracic echocardiography using speckle-tracking method. |
| Reduction in left ventricular filling pressure assessed by change in early mitral inflow velocity (E-wave) and the average of the septal and lateral early diastolic mitral annular velocities ratio (E/e' average) | From enrollment to the end of observational period at 6-month follow-up. | Change in E/e' average, calculated from transthoracic echocardiography by dividing the peak early mitral inflow velocity (E-wave) by the average of the septal and lateral early diastolic mitral annular velocities (e') obtained via tissue doppler imaging. |
| Recovery of impaired myocardial relaxation assessed by change in peak early mitral inflow velocity and peak atrial contraction wave velocity ratio (E/A ratio) | From enrollment to the end of observational period at 6-month follow-up. | Change in E/A ratio, calculated from transthoracic echocardiography by dividing the peak early mitral inflow velocity (E-wave) by the peak atrial contraction velocity (A-wave), both measured via pulsed-wave Doppler in the apical four-chamber view. |
| Reduction in pulmonary artery systolic pressure assessed by change in tricuspid regurgitation maximum gradient (TR max gradient) | From enrollment to the end of observational period at 6-month follow-up. | Change in TR max gradient (mmHg), measured using transthoracic echocardiography by applying continuous wave (CW) doppler to the TR jet to determine the peak velocity, then applying the modified Bernoulli equation. |
| Reduction in left ventricular size assessed by left ventricular end-diastolic volume index (LVEDVi) | From enrollment to the end of observational period at 6-month follow-up. | Change in LVEDVi (mL/m2), calculated from transthoracic echocardiography using Biplane Simpson's method and indexed to body surface area. |
| Reduction in left ventricular wall thickness assessed by posterior (inferolateral) wall diameter (PWd) and interventricular septal diameter (IVSd) | From enrollment to the end of observational period at 6-month follow-up. | Change in PWd (mm) and IVSd (mm), assessed by transthoracic echocardiography using parasternal long-axis view. |
| Improvement in right ventricular systolic function assessed by tricuspid annular plane systolic excursion (TAPSE) | From enrollment to the end of observational period at 6-month follow-up. | Change in TAPSE (mm), assessed by transthoracic echocardiography and measured in the apical 4-chamber view using M-mode placed at the lateral tricuspid annulus. |
| Reduction in the extent of myocardial oedema assessed by cardiac magnetic resonance imaging | Baseline and 6-month follow-up. | Change in the extent of myocardial oedema, assessed by cardiac magnetic resonance imaging scan using T2-weighted imaging and T2-mapping (T2 relaxation times in miliseconds). |
| Remnants of cardiac fibrosis assessed by the extent of late gadolinium enhancement (LGE) | Baseline, 6-month follow-up. | Change in the extent of myocardial LGE (% of left ventricular mass), quantified by cardiac magnetic resonance (CMR). |
| Recovery of coronary microvascular dysfunction assessed by change in angiogenesis-related biomarkers | From enrollment to the end of observational period at 6-month follow-up. | Change in angiogenesis-related biomarker panel composite score, measured using a Luminex multiplex immunoassay. |
| Reduction in cardiac congestion assessed by change in serum levels of natriuretic peptides (NT-proBNP) | From enrollment to the end of observational period at 6-month follow-up. | Change in serum levels of NT-proBNP (ng/L), measured in blood sample by serum biochemical analysis. |
Countries
Slovenia
Contacts
CONTACTMark Jovanović, MD
CONTACTPrincipal Investigator
Outcome results
None listed